Phosphodiesterase-5 inhibitors and their analogues as adulterants of herbal and food products: analysis of the Malaysian market, 2014–16

Abstract

Adulteration of herbal health supplements with phosphodiesterase-5 (PDE-5) inhibitors and their analogues is becoming a worldwide problem. The aim of this study was to investigate herbal and food products sold in the Malaysian market for the presence of these adulterants. Sixty-two products that claim to enhance men's sexual health were sampled between April 2014 and April 2016. These products included unregistered products seized by the Pharmacy Enforcement Division of the Ministry of Health (n = 39), products sent to the National Pharmaceutical Regulatory Agency for pre-registration testing (n = 9) and products investigated under the post-registration market surveillance programme (n = 14). The products were tested against an in-house spectral library consisting of 61 PDE-5 inhibitors and analogues using a validated liquid chromatography-mass spectrometry ion-trap-time-of-flight (LC-MS IT-TOF) method. Thirty-two (82%) of the unregistered products and two (14%) of the registered products were found to be adulterated with at least one PDE-5 inhibitor or analogue, while none of the pre-registration products contained adulterants. A total of 16 different adulterants were detected and 36% of the adulterated products contained a mixture of two or more adulterants. This study has demonstrated that the adulteration of unregistered herbal products in the Malaysian market is an alarming issue that needs to be urgently addressed by the relevant authorities.

Assessing product adulteration ofEurycoma longifolia(Tongkat Ali) herbal medicinal product using DNA barcoding and HPLC analysis

“…2015 ; Bujang et al. 2017 ; Fard and Akhgari 2018 ). Sildenafil (Viagra), tadalafil (cialis) and vardenafil are among the first synthetic PDE-5i drugs to be licensed by the US Food and Drug Administration (FDA) for the treatment of erectile dysfunction, the inability to maintain penile erection during intercourse (Rocha et al.…”

“…This group is under the control of Poison Act 1952 which stipulated that only authorized person such as registered medical practitioners and licensed pharmacists can supply and sell this type of drugs (Bujang et al. 2017 ). Therefore, possession of these types of drugs by unauthorized persons is illegal and punishable by the act.…”

Screening of Phosphodiesterase-5 Inhibitors and Their Analogs in Dietary Supplements by Liquid Chromatography–Hybrid Ion Trap–Time of Flight Mass Spectrometry

“…The retention times and mass errors of all analytes are listed in Table 1, and the extracted ion chromatograms are depicted in Figure 1. (6), piperidinohongdenafil (7), homosildenafil (8), dimethylsildenafil (9), udenafil (10), cyclopentinafil (11), thiosildenafil (12), hydroxythiohomosildenafil (13), thiohomosildenafil (14), dimethylthiosildenafil (15), oxohongdenafil (16), benzylsildenafil (17), hydroxychlorodenafil (18), chlorodenafil (19), nitrodenafil (20), nor-neosildenafil (21), dichlorodenafil (22), vardenafil (23), acetylvardenafil (24), hydroxyvardenafil (25), nor-neovardenafil (26), desulfovardenafil (27), pseudovardenafil (28), tadalafil (29), aminotadalafil (30), acetaminotadalafil (31), demethyltadalafil (32), chloropretadalafil (33), N-octyltadalafil (34), yohimbine (35), mirodenafil (36), thioquinapiperifil (37), xanthoanthrafil (38), and phenolphthalein (39). * indicated the analytes among multiple peaks in the EIC.…”

“…In this regard, various spectrometric and chromatographic methods have been adopted to analyze the illegally added drugs in complex matrices [ 3 , 4 , 5 , 9 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. High-performance liquid chromatography with diode array detection (HPLC–DAD) and liquid chromatography with mass spectrometry (LC–MS) have been previously used to detect PDE-5 inhibitors and their analogs [ 3 , 5 , 7 , 8 , 9 , 10 , 16 , 17 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. When the standards of PDE-5 inhibitors and their analogs are available, HPLC with a UV spectrometer is a simple method for quantitative analysis [ 11 ].…”

Determination of Phosphodiesterase Type 5 Enzyme (PDE-5) Inhibitors and Analogues as Adulterants in Selected Herbal Products using Gas Chromatography–Electron Impact-Mass Spectrometer (GC-EI-MS)

“…For surveillance and monitoring, Control of Drugs and Cosmetics Regulations 1984 was enacted by the Malaysian government to enforce all herbal products that are manufactured, imported and sold in the country to be tested for the presence of adulterants, before registration with the Drug Control Authority of Malaysia (DCA). Unfortunately, even with law enforcement, adulteration of PDE-5 inhibitors in herbal preparations is still prevalent in the Malaysian market (5).…”